NPASS Compound

Natural Product: NPC564716

Natural Product ID	NPC564716
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[5-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-yl]methyl (~{E})-3-(4-hydroxyphenyl)prop-2-enoate
IUPAC Name	[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[5-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-yl]methyl (~{E})-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 72 76 0 0 0 0 0 0 0 0999 V2000 -11.2388 -3.3413 0.1913 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.2018 -2.7849 1.0092 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.0205 -2.3390 0.4335 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7905 -2.4073 -0.9234 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5832 -1.9456 -1.4637 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6020 -1.4168 -0.6701 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3262 -0.9234 -1.1911 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0322 -0.9654 -2.5342 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8130 -0.4943 -3.0365 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5327 -0.5261 -4.2534 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9261 0.0121 -2.1159 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6948 0.5051 -2.4897 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3952 0.4635 -3.8479 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7827 1.0235 -1.5619 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0946 1.0570 -0.2227 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2579 1.5493 0.7555 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0184 2.0865 0.5671 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9520 1.3682 1.3041 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8240 2.1559 1.9902 C 0 0 2 0 0 0 0 0 0 0 0 0 3.9661 1.4582 2.6463 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8322 0.7595 1.8225 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5792 -0.3044 1.0013 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4042 -0.7442 0.9607 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6270 -0.9392 0.1768 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8704 -0.5118 0.1882 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9553 -1.1013 -0.6087 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7663 -2.1706 -1.4516 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7943 -2.7129 -2.1933 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0729 -2.1958 -2.1173 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1264 -2.7278 -2.8572 O 0 0 0 0 0 0 0 0 0 0 0 0 10.2469 -1.1247 -1.2686 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2443 -0.5784 -0.5307 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0020 2.8775 3.0684 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8678 3.5446 3.8980 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9739 3.7559 2.4407 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3101 3.5205 2.9499 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9317 3.5494 0.9612 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8106 4.3576 0.2429 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3498 0.5515 0.1352 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2486 0.0409 -0.7770 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4166 -0.4234 -0.3980 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8487 -1.3547 0.6960 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0401 -1.8085 1.2439 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2860 -1.7457 2.6130 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.8064 -4.0923 -0.5134 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.0285 -3.7943 0.8229 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.7184 -2.5372 -0.4040 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5714 -2.8263 -1.5421 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4584 -2.0226 -2.5209 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7340 -1.3625 -3.2358 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0902 -0.4493 -4.2048 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1606 1.3898 -1.9389 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2965 2.0595 -0.4985 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2826 2.9087 1.2821 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6057 2.2008 3.2124 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5498 0.8182 3.4836 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3571 -1.7710 -0.4455 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0722 0.3340 0.8408 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8024 -2.6240 -1.5617 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6275 -3.5676 -2.8635 H 0 0 0 0 0 0 0 0 0 0 0 0 12.0606 -2.3952 -2.6572 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2407 -0.7020 -1.1922 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3793 0.2724 0.1439 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5380 2.0397 3.6642 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4533 3.6977 4.7767 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2253 4.8223 2.6338 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4503 2.5998 3.2282 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0937 3.9085 0.6356 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4656 5.2721 0.1436 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5965 0.5773 1.1880 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1074 -0.9495 1.3391 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5356 -0.8564 3.0073 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 29 31 1 0 31 32 2 0 19 33 1 0 33 34 1 0 33 35 1 0 35 36 1 0 35 37 1 0 37 38 1 0 15 39 1 0 39 40 2 0 40 41 1 0 6 42 1 0 42 43 2 0 43 44 1 0 43 3 1 0 41 7 1 0 40 11 1 0 37 17 1 0 32 26 1 0 1 45 1 0 1 46 1 0 1 47 1 0 4 48 1 0 5 49 1 0 8 50 1 0 13 51 1 0 14 52 1 0 17 53 1 6 19 54 1 6 20 55 1 0 20 56 1 0 24 57 1 0 25 58 1 0 27 59 1 0 28 60 1 0 30 61 1 0 31 62 1 0 32 63 1 0 33 64 1 1 34 65 1 0 35 66 1 6 36 67 1 0 37 68 1 6 38 69 1 0 39 70 1 0 42 71 1 0 44 72 1 0 M END

Standard InCHIKey	ZSGZLLNDYYOXHG-ACKBESTESA-N
Standard InCHI	InChI=1S/C31H28O13/c1-40-22-8-5-16(10-19(22)33)23-13-21(35)27-20(34)11-18(12-24(27)43-23)42-31-30(39)29(38)28(37)25(44-31)14-41-26(36)9-4-15-2-6-17(32)7-3-15/h2-13,25,28-34,37-39H,14H2,1H3/b9-4+/t25-,28-,29+,30-,31-/m1/s1
SMILES	COC1=CC=C(C2=CC(=O)C3=C(O)C=C(O[C@@H]4O[C@H](COC(=O)/C=C/C5=CC=C(O)C=C5)[C@@H](O)[C@H](O)[C@H]4O)C=C3O2)C=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	608.15	Volume:	581.949 ? Van der Waals volume.
Dense:	1.045	LogP:	2.124 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.06 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.54 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	32.0
TPSA:	205.58 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	6.0	Rings:	5.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.125	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.163	Fsp³:	0.226
MCE-18:	104.421 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.762	Fluc inhibitor:	0.963 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.986 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.997 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.053	Promiscuous compounds:	0.552

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.05	MDCK Permeability:	-5.353
Pgp-inhibitor:	0.034	Pgp-substrate:	0.063
PAMPA:	0.943 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.43
20% Bioavailability (F20%):	0.925	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.021
Plasma Protein Binding (PPB):	91.353%	Volume Distribution (VD):	-0.245
Fu:	7.208% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.116
BSEP inhibitor:	0.714

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.006
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.974
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.361 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

2.021

Half-life (T1/2):

3.823

ADMET: Toxicity

hERG Blockers:	0.075	hERG Blockers (10um):	0.368
Human Hepatotoxicity (H-HT):	0.525	Drug-induced Liver Injury (DILI):	0.983
AMES Toxicity:	0.928	Rat Oral Acute Toxicity:	0.035
Maximum Recommended Daily Dose:	0.425	Skin Sensitization:	0.994
Carcinogencity:	0.358	Eye Corrosion:	0.0
Eye Irritation:	0.314	Respiratory Toxicity:	0.021
Drug-induced Neurotoxicity:	0.004	Ototoxicity:	0.695
Hematotoxicity:	0.054	Drug-induced Nephrotoxicity:	0.472
Genotoxicity:	0.951	RPMI-8226 Immunitoxicity:	0.189
A549 Cytotoxicity:	0.473	Hek293 Cytotoxicity:	0.853
BCF:	0.781 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.616 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.843 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.394 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO960	Phlomis aurea	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO960	Phlomis aurea	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO960	Phlomis aurea	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC564716 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	16732
0.1-0.2	27901
0.2-0.3	3941
0.3-0.4	875
0.4-0.5	293
0.5-0.6	74
0.6-0.7	24
0.7-0.8	1
0.8-0.85	2
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8667	High Similarity	NPC270675
0.8667	High Similarity	NPC195685
0.8421	Intermediate Similarity	NPC472993
0.8191	Intermediate Similarity	NPC472994
0.7423	Intermediate Similarity	NPC80068
0.7423	Intermediate Similarity	NPC477629
0.7216	Intermediate Similarity	NPC209296
0.7157	Intermediate Similarity	NPC480796
0.6774	Remote Similarity	NPC22832
0.6697	Remote Similarity	NPC471030
0.6667	Remote Similarity	NPC473278
0.65	Remote Similarity	NPC46202
0.65	Remote Similarity	NPC64051
0.6373	Remote Similarity	NPC229409
0.6355	Remote Similarity	NPC477895
0.63	Remote Similarity	NPC22062
0.63	Remote Similarity	NPC473634
0.63	Remote Similarity	NPC138811
0.6296	Remote Similarity	NPC217520
0.625	Remote Similarity	NPC85751
0.625	Remote Similarity	NPC19240
0.6211	Remote Similarity	NPC27942
0.62	Remote Similarity	NPC44931
0.619	Remote Similarity	NPC36138
0.6139	Remote Similarity	NPC210073
0.6132	Remote Similarity	NPC223426
0.6122	Remote Similarity	NPC190003
0.6105	Remote Similarity	NPC181712
0.6058	Remote Similarity	NPC473623
0.6038	Remote Similarity	NPC260504
0.6038	Remote Similarity	NPC89809
0.6	Remote Similarity	NPC488089
0.5981	Remote Similarity	NPC484301
0.5962	Remote Similarity	NPC65711
0.5905	Remote Similarity	NPC210961
0.59	Remote Similarity	NPC172807
0.5888	Remote Similarity	NPC101636
0.5888	Remote Similarity	NPC298171
0.5872	Remote Similarity	NPC599948
0.5842	Remote Similarity	NPC254540
0.5833	Remote Similarity	NPC95090
0.5833	Remote Similarity	NPC27408
0.5818	Remote Similarity	NPC470416
0.5806	Remote Similarity	NPC291153
0.5789	Remote Similarity	NPC331652
0.578	Remote Similarity	NPC214621
0.578	Remote Similarity	NPC34267
0.578	Remote Similarity	NPC603856
0.5758	Remote Similarity	NPC243930
0.5752	Remote Similarity	NPC139571
0.5743	Remote Similarity	NPC211594
0.5729	Remote Similarity	NPC39360
0.5729	Remote Similarity	NPC19709
0.5729	Remote Similarity	NPC29763
0.5729	Remote Similarity	NPC210003
0.5726	Remote Similarity	NPC120952
0.5714	Remote Similarity	NPC199172
0.5714	Remote Similarity	NPC470715
0.5714	Remote Similarity	NPC164704
0.57	Remote Similarity	NPC311830
0.567	Remote Similarity	NPC189142
0.567	Remote Similarity	NPC77660
0.5636	Remote Similarity	NPC81042
0.5632	Remote Similarity	NPC223579
0.5614	Remote Similarity	NPC470716
0.5612	Remote Similarity	NPC10205
0.5603	Remote Similarity	NPC198199
0.5556	Remote Similarity	NPC470719
0.5556	Remote Similarity	NPC470717
0.5545	Remote Similarity	NPC607707
0.5508	Remote Similarity	NPC470720
0.5508	Remote Similarity	NPC488078
0.55	Remote Similarity	NPC611303
0.5463	Remote Similarity	NPC476620
0.5446	Remote Similarity	NPC121703
0.5446	Remote Similarity	NPC11468
0.5446	Remote Similarity	NPC601144
0.541	Remote Similarity	NPC35924
0.5408	Remote Similarity	NPC261866
0.5385	Remote Similarity	NPC295625
0.5378	Remote Similarity	NPC488079
0.5321	Remote Similarity	NPC139060
0.5306	Remote Similarity	NPC473043
0.5294	Remote Similarity	NPC486578
0.5294	Remote Similarity	NPC605067
0.5268	Remote Similarity	NPC179862
0.5214	Remote Similarity	NPC488087
0.5196	Remote Similarity	NPC191306
0.5196	Remote Similarity	NPC204937
0.5196	Remote Similarity	NPC285197
0.5185	Remote Similarity	NPC204693
0.5185	Remote Similarity	NPC186816
0.5135	Remote Similarity	NPC479766
0.5135	Remote Similarity	NPC486577
0.5133	Remote Similarity	NPC218161
0.5126	Remote Similarity	NPC488086
0.5102	Remote Similarity	NPC157898
0.5098	Remote Similarity	NPC471405
0.5093	Remote Similarity	NPC473512
0.5093	Remote Similarity	NPC129827
0.5091	Remote Similarity	NPC477628
0.5089	Remote Similarity	NPC479765
0.5083	Remote Similarity	NPC298666
0.5081	Remote Similarity	NPC25946
0.5045	Remote Similarity	NPC483707
0.5045	Remote Similarity	NPC606657

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC564716 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4215
0.1-0.2	4836
0.2-0.3	86
0.3-0.4	8
0.4-0.5	3
0.5-0.6	1
0.6-0.7	0
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7216	Intermediate Similarity	NPD7054	Phase 4
0.5446	Remote Similarity	NPD7472	Pre-clinical

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data